Construction And Application Of AIE Compounds With Lipid Droplets Recognition/Photodynamic Activity

With the improvement of economy,people's living standards are improving,and diseases caused by obesity have attracted more and more attention.Obesity is caused by the accumulation of excess fat in the body,which is due to the excess of energy intake over energy expenditure.Obesity can lead to dyslipidemia,which further increases the risk of pancreatitis,diabetes and cardiovascular disease.Lipid droplets(LDs),composed of triglycerides and cholesterol,are intracellular dynamic organelles present in adipocytes,adrenal cortices,hepatocytes,and other adipose tissue in eukaryotes.They play an important role in regulating the storage and hydrolysis of neutral lipids.Excessive accumulation and abnormal metabolism of LDs in cells lead to obesity and a series of diseases,such as fatty liver,coronary heart disease and diabetes,which are the diseases with the highest mortality in the world.Therefore,the detection and tracking of LDs can provide useful value for biomedical research and biotechnology applications.Fluorescence imaging is considered as an indispensable technology for biomedical research due to its high sensitivity,excellent temporal and spatial resolution,non-invasive properties,and fast real-time response,which is conducive to visualizing biological processes occurring in living organisms and intuitively understanding complex biological structures.The traditional fluorescence materials caused quenching at high concentration limits its practical application.In 2001,Tang Benzhong put forward the concept of aggregation-induced emission(AIE),which made up for this deficiency.Because of their high stoke's shift,high fluorescence quantum yield,AIE fluorescence materials have the ability to detect targets in aqueous solution.In view of this,by constructing AIE system,we synthesized a series of AIE materials,and characterized them by ¹H NMR,¹³C NMR,high resolution mass spectrometry(ESI-MS)and IR.The phenomenon of was AIE verified by fluorescence spectrum,and the orbital of compounds was preliminarily analyzed by theoretical calculation(DFT).Subsequently,its targeting of LDs in cells and preliminary studies in other biological and medical fields was carried out.We introduced follows through the following 5 chapters:1.By installing different types of rotors in the ACQ compounds,we constructed the AIE system(A2-A4,B1-B3).By changing different electron donors(D)or changing the electron-withdrawing group(A) receptor,realized gradually enhanced donor-receptor(D-A)interaction, further realized the tunable emission wavelength,covered almost all rigion of visible light(400-780 nm).Theoretical calculation shows that the value of maximum absorption wavelength of the constructed AIE system is consistent with the change of energy gap((35)E_H-L).The toxicity test found that the constructed AIE system had good biocompatibility. These AIE system have the ability to targeting LDs in lipid-rich cancer cells(PC12 cells),and has a good colocalization coefficient with the commercial lipid-targeting dye BODIPY 493/503.Interestingly,as a hydrophobic compound,B3 exhibits well photostability and can distinguish blood from hyperlipidemia patient and normal people.2.In order to recognize the LDs on the surface of the trachea,to realize the visualization of the trachea under microscope,three TPA-based NIR compounds were designed and synthesized.By observing the morphological characteristics of trachea further reflect expression level of chitin,thus reflecting the success of gene knockout technology.All compounds consist of two electrondonating units(D₁,D₂)and one electron-accepting(A),which were connected by?-bridge and formed the D₁-D₂-?-A structure.The photophysical properties show that they are NIR fluorescent materials with AIE properties.These AIE compounds have a high ability to target LDs in PC12 cells and corpus adiposum.Due to numbers of LDs are secreted on the surface of the trachea of locusts,thus realizing the visualization of the trachea.In addition,these compounds can effectively produce reactive oxygen species(ROS)under white light irradiation,and their application in PDT of cancer cells has been studied. Subsequently,the transfer of ROS from LDs(trioctanoin)to cytoplasmic matrix(PBS)was simulated,further speculating the potential relationship between photodynamic drugs targeting LDs and apoptosis of cells.3.Three TPA-based red/NIR fluorophores were prepared and synthesized.These molecules had D₁-D₂-?-A structures.Different charge transfer properties were realized by changing different D₂(phenyl,thiophene or furan rings),further realized the tunability of emission wavelength in NIR region.Theoretical calculation show that the change of HOMO-LUMO energy band is consistent with its absorption spectrum,compounds with low?E_S1-T1 endows its application in the PDT.In biological applications, these AIEgens showed good LDs targeting ability in cells,in vitro adipose tissues of locusts and oil-bearing crops,and were further applied in model organisms,such as zebrafish and Caenorhabditis elegans.In addition,the compounds were preliminarily studied on PDT of SMMC-7721 cancer cells,and the results showed that these compounds had low dark toxicity and strong killing ability to cancer cells under white light,indicating their application value in PDT.This study is the first to report the imaging and application of TPA-based AIE compounds in typical model organisms.